Single-cell analysis characterizes PLK1 as a promoter of immunosuppressive tumor microenvironment in LUAD

PLK1 (Polo-like kinase 1) plays a critical role in cancer progression of lung adenocarcinoma (LUAD).

Recent studies have demonstrated that targeting PLK1 improves the efficacy of immunotherapy, indicating its important role in the regulation of tumor immunity.

However, the correlation between PLK1 and tumor microenvironment (TME) is poorly understood.

Here, using genetically engineered mouse model and single-cell RNA-seq analysis, we report that PLK1 promotes a general immunosuppressive TME in LUAD characterized with impaired tumor-infiltrating lymphocytes, enhanced M2 polarization and suppression of antigen presentation process.

Mechanistically, elevated PLK1 coincides with increased secretion of CXCL2 cytokine, which promotes M2 polarization of macrophages and decreases expression of class II major histocompatibility complex (MHC-II) in professional antigen-presenting cells.

Furthermore, PLK1 negatively regulates MHC-II expression in cancer cells, which has been shown to be associated with poor tumor immunity and patients’ outcomes.

Taken together, our results reveal PLK1 as a novel modulator of TME in LUAD and provide possible therapeutic interventions.

SIGNIFICANCE: The characterization of PLK1 as a promoter of immunosuppressive tumor microenvironment enhances our understanding of PLK1’s role in anti-tumor immunity and supports the idea of targeting PLK1 in cancer treatment.